Diaphragm Neurostimulation Assisted Ventilation in Critically Ill Patients.

Diaphragm neurostimulation consists of placing electrodes directly on or in proximity to the phrenic nerve(s) to elicit diaphragmatic contractions. Since its initial description in the 18th century, indications have shifted from cardiopulmonary resuscitation to long-term ventilatory support. Recently, the technical development of devices for temporary diaphragm neurostimulation has opened up the possibility of a new era for the management of mechanically ventilated patients. Combining positive pressure ventilation with diaphragm neurostimulation offers a potentially promising new approach to the delivery of mechanical ventilation which may benefit multiple organ systems. Maintaining diaphragm contractions during ventilation may attenuate diaphragm atrophy and accelerate weaning from mechanical ventilation. Preventing atelectasis and preserving lung volume can reduce lung stress and strain and improve homogeneity of ventilation, potentially mitigating ventilator-induced lung injury. Furthermore, restoring the thoracoabdominal pressure gradient generated by diaphragm contractions may attenuate the drop in cardiac output induced by positive pressure ventilation. Experimental evidence suggests diaphragm neurostimulation may prevent neuroinflammation associated with mechanical ventilation. This review describes the historical development and evolving approaches to diaphragm neurostimulation during mechanical ventilation and surveys the potential mechanisms of benefit. The review proposes a research agenda and offers perspectives for the future of diaphragm neurostimulation assisted mechanical ventilation for critically ill patients.

The oncologic efficacy of extended resections for lung cancer.

Extended lung resections for T3-T4 non-small-cell lung cancer remain challenging. Multimodal management is mandatory in multidisciplinary tumor boards, and here the determination of resectability is key. Long-term oncologic efficacy depends mostly on complete resection (R0) and the extent of N2 disease. The development of novel innovative treatments (targeted therapy and immune checkpoint inhibitors) sets interesting perspectives to reinforce current therapeutic options in the induction and adjuvant setting.

Is surgical rib fixation in patients aged more than 65 years old associated with worse outcomes compared to younger patients? A retrospective single-center study.

BACKGROUND: There is no robust data regarding rib fixation in elderly patients. The aim of this study is to compare the postoperative outcomes of patients aged less and more than 65 years old. METHODS: Patients operated from January 2012 to December 2018 were retrospectively analyzed. The following data were collected: age, sex, comorbidities, smoking habit, Injury Severity Score (ISS), number of fractured ribs, indication for surgery, associated injuries, time from trauma to surgery, number of fixed ribs, intrathoracic injuries, duration of intubation, ICU stay, postoperative cardiopulmonary complications, blood transfusion, overall and 30-day mortality, length of stay. RESULTS: There was no difference regarding the ISS (p = 0.09), the number of rib fractures (p = 0.291), the indication for surgery, the number of fixed ribs (p = 0.819), the ICU stay (p = 0.096), the postoperative intubation duration (p = 0.059), the cardiopulmonary complications (p = 0.273) and perioperative blood transfusions (p = 0.34). Elderly patients presented more postoperative cognitive complications (p < 0.001). There was no difference in terms of overall mortality (p = 0.06) and 30-day mortality (p = 0.69). Elderly patients stayed longer in the hospital (p < 0.001). CONCLUSIONS: The outcomes of rib fixation in the elderly patients are comparable to younger patients. However, elderly patients experience more frequently postoperative cognitive complications and their hospitalizations are longer.

Persistence of Intraluminal Thrombus Makes Saccular Aneurysm More Biologically Active than Fusiform in an Experimental Rat Model.

INTRODUCTION: Saccular aneurysms are thought to have a worse prognosis than fusiform aneurysms in humans, due to hemodynamic reasons. However, data comparing hemodynamic and biology in saccular and fusiform aneurysms are lacking. The main objective was to evaluate the impact of aneurysm morphology on intra-luminal thrombus (ILT) formation and activity. METHODS: Forty Lewis rats were ran-domly divided into 2 groups of 20: "saccular" (Group A) and "fusiform" (Group B) aneurysms. Decellularized thoracic aortas from guinea pigs were xenografted to create saccular or fusiform aneurysms. Final imaging evaluation of the aneurysms was carried out during the third week, by quantitative Doppler ultrasound and magnetic resonance imaging. Assays of myeloperoxidase (MPO), platelet factor 4 (PF4), advanced oxidation protein products (AOPPs) iron and matrix metallopeptidase-9 (MMP-9) were performed as biological criteria. RESULTS: Quantitatively, saccular aneurysms are characterized by a more thicker ILT, lower inflow velocities and more important relative backflow velocities as compared to fusiform aneurysms. Compared to fusiform, saccular aneurysms released significantly more MPO (p = 0.004), PF4 (p = 0.02), AOPPs (p < 0.002), iron (p < 0.0001) and MMP-9 (p < 0.04). CONCLUSION: Experimental saccular and fusiform aneurysms show differential specific hemodynamics, which seem to impact the histology and the biology of the ILT in each type of aneurysm.

A Single-Center Experience of Osteosynthesis Material Infection after Rib Fixation for Blunt Trauma.

INTRODUCTION: There is no data regarding the incidence and treatment of deep infection affecting the surgical implants after rib fixation. The aim of this study is to share our experience in the management of infected material after surgical rib fixation. METHODS: The medical records of operated patients from January 2012 to December 2018 were retrospectively analyzed. RESULTS: Three patients out of 87 (3.44%) developed an infection. One patient was treated conservatively and two patients were operated for hardware removal. CONCLUSIONS: The lack of evidence prompts for the design of surgical databases to share experience and enhance available data.

Postero-apical thoracic schwannoma with cervical extension resected by complete video-assisted thoracoscopic surgery.

Schwannomas or neurilemmomas are benign tumors developed from the peripheral nervous system. Complete video-assisted thoracic surgery (cVATS) has set itself over the years as the preferred approach for the removal of small mediastinal neurogenic tumors. However, in case of apical location, complete VATS seems challenging because of proximity with the subclavian artery and/or elements of the brachial plexus. In case of a cVATS procedure, some authors prefer enucleation instead of resection, with a higher risk of relapse. We present two cases of cVATS resection of thoracic apical schwannomas.

Tracheal replacement.

Tracheal reconstruction is one of the greatest challenges in thoracic surgery when direct end-to-end anastomosis is impossible or after this procedure has failed. The main indications for tracheal reconstruction include malignant tumours (squamous cell carcinoma, adenoid cystic carcinoma), tracheoesophageal fistula, trauma, unsuccessful surgical results for benign diseases and congenital stenosis. Tracheal substitutes can be classified into five types: 1) synthetic prosthesis; 2) allografts; 3) tracheal transplantation; 4) tissue engineering; and 5) autologous tissue composite. The ideal tracheal substitute is still unclear, but some techniques have shown promising clinical results. This article reviews the advantages and limitations of each technique used over the past few decades in clinical practice. The main limitation seems to be the capacity for tracheal tissue regeneration. The physiopathology behind this has yet to be fully understood. Research on stem cells sparked much interest and was thought to be a revolutionary technique; however, the poor long-term results of this approach highlight that there is a long way to go in this research field. Currently, an autologous tissue composite, with or without a tracheal allograft, is the only long-term working solution for every aetiology, despite its technical complexity and setbacks.

Exploring antibody-dependent adaptive immunity against aortic extracellular matrix components in experimental aortic aneurysms.

BACKGROUND: Recent evidence suggests that adaptive immunity develops during abdominal aortic aneurysm evolution. Uncertainties remain about the antigens implicated and their role in inducing rupture. Because antigens from the extracellular matrix (ECM) have been suspected, the aim of this experimental study was to characterize the role of adaptive immunity directed against antigens from the aortic ECM. METHODS: In a first step, an experimental model of abdominal aortic aneurysm rupture based on adaptive immunity against the ECM was developed and characterized. Forty 4-week-old male Lewis rats were divided into two groups. In the ECM group (n = 20), rats were presensitized against the guinea pig aortic ECM before implantation of a decellularized aortic xenograft (DAX). In the control group (n = 20), rats were not presensitized before DAX implantation. In each group, half the rats were sacrificed at day 3 to analyze early mechanisms involved after DAX implantation. In a second step, we aimed to assess which ECM component was most efficient in inducing rupture. For this purpose, the nonfibrillar and fibrillar ECM components were sequentially extracted from the guinea pig aortic wall. Forty Lewis rats were then divided into four groups. Each group was presensitized against one ECM component (structural glycoproteins and proteoglycans, collagen, elastin alone, and elastin-associated glycoproteins) before DAX implantation. Apart from those that experienced rupture, rats were sacrificed at day 21. Xenografts were harvested for histologic, immunofluorescence, and conditioned medium analyses. RESULTS: In total, early aortic rupture occurred in 80% of the ECM group vs 0% of the control group (P < .001). In the ECM group, major circumferential immunoglobulin deposits were observed in combination with the C3 complement fraction, without cell infiltration. Conditioned medium analysis revealed that matrix metalloproteinase 9 and myeloperoxidase levels and elastase activities were significantly increased in this group. Immunofluorescence analysis demonstrated that myeloperoxidase co-localized with tissue-free DNA and histone H4, highlighting local neutrophil activation and formation of neutrophil extracellular traps. Following differential presensitization, it appeared that rats presensitized against structural glycoproteins and proteoglycans were significantly more susceptible to rupture after DAX implantation. CONCLUSIONS: Stimulating adaptive immunity against the aortic ECM, especially structural glycoproteins and proteoglycans, triggers rupture after DAX implantation. Further studies are needed to assess the precise proteins involved.

Translational Relevance and Recent Advances of Animal Models of Abdominal Aortic Aneurysm.

Human abdominal aortic aneurysm (AAA) pathophysiology is not yet completely understood. In conductance arteries, the insoluble extracellular matrix, synthesized by vascular smooth muscle cells, assumes the function of withstanding the intraluminal arterial blood pressure. Progressive loss of this function through extracellular matrix proteolysis is a main feature of AAAs. As most patients are now treated via endovascular approaches, surgical AAA specimens have become rare. Animal models provide valuable complementary insights into AAA pathophysiology. Current experimental AAA models involve induction of intraluminal dilation (nondissecting AAAs) or a contained intramural rupture (dissecting models). Although the ideal model should reproduce the histological characteristics and natural history of the human disease, none of the currently available animal models perfectly do so. Experimental models try to represent the main pathophysiological determinants of AAAs: genetic or acquired defects in extracellular matrix, loss of vascular smooth muscle cells, and innate or adaptive immune response. Nevertheless, most models are characterized by aneurysmal stabilization and healing after a few weeks because of cessation of the initial stimulus. Recent studies have focused on ways to optimize existing models to allow continuous aneurysmal growth. This review aims to discuss the relevance and recent advances of current animal AAA models. VISUAL OVERVIEW: An online visual overview is available for this article.

Emergency Endovascular Interventions for Ruptured Descending Thoracic Aortic Aneurysm.

BACKGROUND: Ruptured descending thoracic aortic aneurysm (rDAA) is a rare but devastating condition. Open aortic surgery which uses cardiopulmonary bypass is associated with a high mortality. Thoracic endovascular aortic repair (TEVAR) is a less-invasive approach for which it remains unclear whether outcomes are superior or equivalent to open aortic surgery. In this study, we report our early and midterm outcomes with TEVAR for rDAA. METHODS: This is an observational, retrospective, single-center study which included patients with rDAA and treated by TEVAR. The main objective was the 30-day in-hospital mortality. Secondary end points were 30-day in-hospital morbidity, 2-year mortality, and technical problems encountered during procedures. RESULTS: Twenty-five patients were included: 14 men and 11 women with a median age of 76 years (69-82 years). Thirty-day in-hospital mortality rate was 36% (95% confidence interval [CI], 20.6-57.9; n = 9), and the 2-year mortality rate was 44% (95% CI, 27.94-66.72; n = 11). Fifteen patients (60%) presented at least 1 major complication, and 8 of those patients had a second surgery because of it. There were 9 technical problems encountered that required additional open procedures to successfully deploy the aortic stent graft: lack of vascular access in 2 cases (8%), short proximal neck in 3 cases (12%), and short distal neck in 4 cases (16%). CONCLUSIONS: Mortality and morbidity remain high in patients treated for rDAA by TEVAR. Nonetheless, TEVAR remains an interesting alternative to open aortic surgery especially for older patients with a poor general health and functional status.

Unusual Acute Onset of Abdominal Aortic Endograft Infection by Propionibacterium acnes after Coil Embolization for Type II Endoleak.

Propionibacterium acnes, an anaerobic gram-positive bacillus that inhabits the skin, has rarely been incriminated in abdominal aortic endograft infection. It is usually responsible for typical delayed and low-grade postoperative infections. We report the case of a 66-year-old patient who developed acute P. acnes aortic stent-graft infection 9 days after percutaneous embolization for type II endoleak. The stent graft had been implanted 2 years before. Because of persistent signs of sepsis and discovery of a posterior periaortic abscess formation on the computed tomography scan, removal of the stent graft was necessary. Despite being described as a low virulence and slow growth bacteria, P. acnes was responsible for acute onset of postoperative infection with extensive life-threatening damages necessitating multiple interventions associated with long-term antibiotherapy.

Size-matching in lung transplantation by computed tomography for end-stage interstitial disease: a retrospective analysis.

Background: Size matching between donors and recipients is a major issue in lung transplantation (LTx), especially in patients with restrictive lung disease (RLD). This study aims to evaluate computed tomography (CT) as an additional method for defining the total lung capacity (TLC) in patients with end-stage interstitial disease awaiting LTx. Methods: Clinical data and CT scans from patients who underwent a first LTx from January 2014 to July 2018 in Bichat Hospital, Paris, were prospectively included in a database. CT TLC (ctTLC) was retrospectively calculated after semi-automatic contouring of the parenchyma and compared with measured TLC (mTLC) and predicted TLC (pTLC) values. Results: The study group included 89 patients (male:female =68:21; mean age, 59.5±10.0 years). The time between pulmonary function tests (PFTs) and CT scan was 162±270 days [median, 67 days; interquartile range (IQR), 0-233 days]. ctTLC was inferior to mTLC and pTLC (respectively 2,979±1,001 mL, 3,530±1,077 and 6,381±955 mL, P<0.001). The relative difference between CT lung volume (ctLV) and measured lung volume (mLV) was higher on the left than on the right side (25.4% vs. 16.3%, respectively, P=0.11). After exclusion of two outliers, we found a significant correlation between ctTLC and mTLC (r=0.762, P<0.001). Conclusions: CT volume is a feasible method to assess TLC in patients with end-stage interstitial disease awaiting LTx. This study highlights potential size-mismatch for graft selection before LTx and opens the perspective of a prospective trial evaluating impact of size-matching by donor-recipient (D-R) ctTLC ratio on postoperative outcomes.

How safe is lung transplantation in patients of 65 years or older? A single-center retrospective cohort.

INTRODUCTION: With increasing experience in high-volume centers, age alone should not be an absolute contra-indication to lung transplantation (LT) but be considered as part of the patient's initial characteristics. The objective of this study is to provide early and long-term outcomes of LT in recipients aged 65 or older, compared with their younger counterparts. METHODS: This is a retrospective study, including all patients undergoing LT in Bichat Hospital (Paris, France) from January 2014 to March 2019. Two groups were defined depending on the patients' age when they were transplanted: patients older than 65 were defined as the "elderly group" and patients younger than 65 years old were defined as the « younger group ¼. Primary endpoint was 90-day mortality. Secondary endpoints included 1-year mortality, 1-year FEV1 (forced expiratory volume in one second), and 5-year overall survival. RESULTS: From September 2014 to March 2019, 22 patients were included in the "elderly group" and 213 were included in the « younger group ¼. The elderly group had more single LT (SLT) (82% vs. 29%, p < 0.001), with a shorter cold ischemic time (243 min vs. 310 min, p = 0.001) and a lower rate of early humoral rejection (9% vs. 30%, p = 0.045) compared to the younger group. Ninety-day mortality was not significantly different between elderly and younger group (9% vs. 14%, p = 0.95, respectively), nor were 1-year mortality (23% vs. 25%, p = 0.9, respectively) and 5-year overall survival. Six months after LT, FEV1 was significantly better in the elderly group compared to the younger group (77.0% vs. 65.5%, p = 0.037 respectively), but the difference did not reach statistical significance after one year (78.5 vs. 68.3%, p = 0.18 respectively). CONCLUSION: Elderly patients underwent more frequently single LT, and achieved similar short and long term postoperative outcomes compared to their younger counterparts. LT for patients 65 years or older should be routinely considered when carefully selected.

Outcomes and costs with the introduction of robotic-assisted thoracic surgery in public hospitals.

Robotic-assisted thoracic surgery (RATS) is an effective treatment of non-small cell lung cancer (NSCLC) but the effects of its implementation in university hospital networks has not been described. We analyzed the early clinical outcomes, estimated costs, and revenues associated with three robotic systems implemented in the Paris Public Hospital network. A retrospective study included patients who underwent RATS for NSCLC in 2019 and 2020. Ninety-day morbidity, mortality, hospital costs, and hospital revenues were described. Economic analyses were conducted either from the hospital center or from the French health insurance system perspectives. Cost drivers were tested using univariate and multivariable analyses. Sensitivity analyses were performed to assess uncertainty over in-hospital length of stay (LOS), number of robotic surgeries per year, investment cost, operating room occupancy time, maintenance cost, and commercial discount. The study included 188 patients (65.8 ± 9.3 years; Charlson 4.1 ± 1.4; stage I 76.6%). Median in-hospital LOS was 6 days [5-9.5], 90-day mortality was 1.6%. Mean hospital expenses and revenues were €12,732 ± 4914 and €11,983 ± 5708 per patient, respectively. In multivariable analysis, factors associated with hospital costs were body mass index, DLCO, major complications, and transfer to intensive care unit. Sensitivity analyses showed that in-hospital LOS (€11,802-€15,010) and commercial discounts on the list price (€11,458-€12,732) had an important impact on costs. During the first 2 years following the installation of three robotic systems in Paris Public Hospitals, the clinical outcomes of RATS for NSCLC have been satisfactory. Without commercial discount, hospital expenses would have exceeded hospital revenues.Clinical registration number CNIL, N°2221601, CERC-SFCTCV-2021-07-20-Num17_MOPI_robolution.

Impact of surgical approach on 90-day mortality after lung resection for nonsmall cell lung cancer in high-risk operable patients.

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

Swiss Pilot Low-Dose CT Lung Cancer Screening Study: First Baseline Screening Results.

This pilot study conducted in Switzerland aims to assess the implementation, execution, and performance of low-dose CT lung cancer screening (LDCT-LCS). With lung cancer being the leading cause of cancer-related deaths in Switzerland, the study seeks to explore the potential impact of screening on reducing mortality rates. However, initiating a lung cancer screening program poses challenges and depends on country-specific factors. This prospective study, initiated in October 2018, enrolled participants meeting the National Lung Cancer Study criteria or a lung cancer risk above 1.5% according to the PLCOm2012 lung cancer risk-model. LDCT scans were assessed using Lung-RADS. Enrollment and follow-up are ongoing. To date, we included 112 participants, with a median age of 62 years (IQR 57-67); 42% were female. The median number of packs smoked each year was 45 (IQR 38-57), and 24% had stopped smoking before enrollment. The mean PLCOm2012 was 3.7% (±2.5%). We diagnosed lung cancer in 3.6% of participants (95%, CI:1.0-12.1%), with various stages, all treated with curative intent. The recall rate for intermediate results (Lung-RADS 3,4a) was 15%. LDCT-LCS in Switzerland, using modified inclusion criteria, is feasible. Further analysis will inform the potential implementation of a comprehensive lung cancer screening program in Switzerland.

Outcome Analysis of Treatment Modalities for Thoracic Sarcomas.

BACKGROUND: Primary chest wall sarcomas are a rare and heterogeneous group of chest wall tumors that require multimodal oncologic and surgical therapy. The aim of this study was to review our experience regarding the surgical treatment of chest wall sarcomas, evaluating the short- and long-term results. METHODS: In this retrospective single-center study, patients who underwent surgery for soft tissue and bone sarcoma of the chest wall between 1999 and 2018 were included. We analyzed the oncologic and surgical outcomes of chest wall resections and reconstructions, assessing overall and recurrence-free survival and the associated clinical factors. RESULTS: In total, 44 patients underwent chest wall resection for primary chest wall sarcoma, of which 18 (41%) received surgery only, 10 (23%) received additional chemoradiotherapy, 7% (3) received surgery with chemotherapy, and 30% (13) received radiotherapy in addition to surgery. No perioperative mortality occurred. Five-year overall survival was 51.5% (CI 95%: 36.1-73.4%), and median overall survival was 1973 days (CI 95% 1461; -). As determined in the univariate analysis, the presence of metastasis upon admission and tumor grade were significantly associated with shorter survival (p = 0.037 and p < 0.01, respectively). Five-year recurrence-free survival was 71.5% (95% CI 57.6%; 88.7%). Tumor resection margins and metastatic disease upon diagnosis were significantly associated with recurrence-free survival (p < 0.01 and p < 0.01, respectively). CONCLUSION: Surgical therapy is the cornerstone of the treatment of chest wall sarcomas and can be performed safely. Metastasis and high tumor grade have a negative influence on overall survival, while tumor margins and metastasis have a negative influence on local recurrence.

Role of RAPID score and surgery in the management of pleural infection: a single center retrospective study.

Background: The RAPID [Renal (urea level), Age, Pleural fluid purulence, source of Infection and Denutrition (albumin level)] score classifies patients with pleural infection according to mortality risk at 3 months. This study aims to assess the applicability of this score in a thoracic surgery department and to determine the impact of surgery in the management of pleural infection depending on the Rapid score. Methods: In this single center retrospective study, patients managed for pleural infection, from January 1st 2013 to June 30th 2019, were included. The primary endpoint was the probability of survival at 6 months and 12 months depending on the RAPID score. Secondary endpoint was the probability of survival at 6 and 12 months in patients who had surgeries (surgical treatment group) and patients who didn't have surgery (medical treatment group). Results: Seventy-four patients were included, with a median age of 54.5 years. According to the RAPID score, the low-, medium- and high-risk groups had 30, 30 and 14 patients respectively. The probability of survival at 6 and 12 months in the low- and medium-risk groups were both 0.967 [95% confidence index (CI95): 0.905-1] whereas, the probabilities of survival at 6 and 12 months in the high-risk group was significantly lower at 0.571 (CI95: 0.363-0.899) and 0.357 (CI95: 0.177-0.721) respectively (P<0.0001). The probabilities of survival at 6 months and 12 months in the medical treatment group was 0.875 (CI95: 0.786-0.974) and 0.812 (CI95: 0.704-0.931) respectively compared to the surgical treatment group where probabilities of survival at 6 and 12 months were both 0.923 (CI95: 0.826-1) (P=0.26). Conclusions: In our study, patients with pleural infection, classified as high-risk according to the RAPID score, had a lower survival rate compared to low- and medium-risk patients. No difference in survival rate was found between patients classified as low- and medium-risk. In selected patients, surgical management seems to decrease mortality compared to exclusive medical management: this result should be confirmed in larger prospective studies.

Anatomic lung resection after immune checkpoint inhibitors for initially unresectable advanced-staged non-small cell lung cancer: a retrospective cohort analysis.

Background: Patients with initially unresectable advanced non-small cell lung cancer (NSCLC) might experience prolonged responses under immune checkpoint inhibitors (ICIs). In this setting, Multidisciplinary Tumor Board (MTB) seldomly suggest surgical resection of the primary tumor with the ultimate goal to eradicate macroscopic residual disease. Our objective was to report the perioperative outcomes of patients who underwent anatomic lung resection in these infrequent circumstances. Methods: We set a retrospective multicentric single arm study, including all patients with advanced-staged initially unresectable NSCLC (stage IIIB to IVB) who received systemic therapy including ICIs and eventually anatomical resection of the primary tumor in 10 French thoracic surgery units from January 2016 to December 2020. Coprimary endpoints were in-hospital mortality and morbidity. Secondary endpoints were the rate of complete resection of the pulmonary disease, major pathologic response, risk factors associated with post-operative complications, and overall survival. Results: Twenty-one patients (median age 64, female 62%) were included. Eighteen patients (86%) progressed after first line chemotherapy and received second line ICI. The median time between diagnosis and surgery was 22 months [interquartile range (IQR) 18-35 months]. Minimally-invasive approach was used in 10 cases (48%), with half of these requiring conversion to open thoracotomy. Nine patients (43%) presented early post-operative complications, and one patient died from broncho-pleural fistula one month after surgery. Rates of complete resection of the pulmonary disease and major pathologic response were 100% and 43%, respectively. In univariable analysis, diffusing capacity for carbon monoxide (DLCO) was the only factor associated with the occurrence of postoperative complications (P=0.027). After a median follow-up of 16.0 months after surgery (IQR, 12.0-30.0 months), 19 patients (90%) were still alive. Conclusions: Anatomic lung resections appear to be a reasonable option for initially unresectable advanced NSCLC experiencing prolonged response under ICIs. Nonetheless, minimally invasive techniques have a low applicability and post-operative complications remains higher in patients who had lower DLCO values. The late timing of surgery may also contribute to complications.

Change in Right-to-Left Shunt Fraction in Patients with Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Endarterectomy.

BACKGROUND: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH) with accessible lesions. Breathing pure oxygen (hyperoxia) during right heart catheterization (RHC) allows for the calculation of the right-to-left shunt fraction (Qs/Qt). In the absence of intracardiac shunt, Qs/Qt can be used as a marker of ventilation-perfusion mismatch in patients with CTEPH. This study involved investigating Qs/Qt after PEA and its relation to other disease-specific outcomes. STUDY DESIGN AND METHODS: This study is a retrospective study that focuses on patients with operable CTEPH who had Qs/Qt assessment during RHC before and 1 year after PEA. Additionally, 6 min walking distance (6MWD), WHO functional class (WHO-FC), and NT-proBNP were assessed to calculate a four-strata risk score. RESULTS: Overall, 16 patients (6 females) with a median age of 66 years (quartiles 55; 74) were included. After PEA, an improvement in mean pulmonary artery pressure (38 [32; 41] to 24 [18; 28] mmHg), pulmonary vascular resistance (5.7 [4.0; 6.8] to 2.5 [1.4; 3.8] WU), oxygen saturation (92 [88; 93]% to 94 [93; 95]%), WHO-FC, and risk score was observed (all p < 0.05). No improvement in median Qs/Qt could be detected (13.7 [10.0; 17.5]% to 13.0 [11.2; 15.6]%, p = 0.679). A total of 7 patients with improved Qs/Qt had a significant reduction in risk score compared to those without improved Qs/Qt. CONCLUSION: PEA did not alter Qs/Qt assessed after 1 year in operable CTEPH despite an improvement in hemodynamics and risk score, potentially indicating a persistent microvasculopathy. In patients whose shunt fraction improved with PEA, the reduced shunt was associated with an improvement in risk score.